biostudies-literatureUnknown10(51)Lee UPrevious evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on <i>Drosophila melanogaster</i> tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene <i>HP6</i>/<i>Umbrea</i> as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple <i>Drosophila</i> species, we show that <i>HP6/Umbrea</i> was inserted near a preexisting, longScience advanceseadn6625https://www.ebi.ac.uk/biostudies/studies/S-EPMC11654672biostudies-literatureThe three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence.PMC11654672Arsala DLi CSobreira DRZhou QChen JAndolfatto PLong MXia SZhang LAli MEres ISvetec NLanger CBZhao LReilly PGuzzetta AEmerson JJSosa DLee UfalseThe three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence.Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on <i>Drosophila melanogaster</i> tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene <i>HP6</i>/<i>Umbrea</i> as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple <i>Drosophila</i> species, we show that <i>HP6/Umbrea</i> was inserted near a preexisting, long2024-01-01T00:00:00Z2024 Dec2025-04-22T10:40:39.786Z2025-04-05T23:43:16.969ZS-EPMC116546723969342510.1126/sciadv.adn6625